Acute Respiratory Failure (ARF) requiring mechanical ventilation affects 1.1 million of the 4.4 million people admitted to US Intensive Care Units (ICU) every year. Patients with ARF experience deconditioning, muscle weakness, joint contractures, dyspnea, depression, and reduced health-related quality of life, all of which may contribute to prolonged hospitalization and increased costs. Patients with ARF average 15 hospital days with median costs of $30,000. Critical care rehabilitative therapy for patients with ARF is not uniform in its content, timing or the acceptance of its safety. Our published data indicate that Standardized Rehabilitation Therapy, initiated in the ICU, is feasible and safe. The pilot showed a trend in reduced hospital stay, but functional outcomes were not determined. Therefore, for the acceptance of Standardized Rehabilitation Therapy in US hospitals to advance, this study will demonstrate that Standardized Rehabilitation Therapy for patients with ARF reduces hospital stay through immediate improvement in functional capacity and functional performance. Mechanistically, it is understood that patients with ARF exhibit acute inflammation and since rehabilitation increases functional outcomes and lowers biomarkers of inflammation in heart failure and the frail aging, we will determine whether the anticipated improvements in ARF patient outcomes are associated with a reduction in biomarkers of inflammation. The proposed study will test the following hypotheses: 1) Standardized Rehabilitation Therapy will shorten hospital stay in patients with ARF; 2) Standardized Rehabilitation Therapy will improve objective functional measures and quality of life at 6 months post-enrollment; 3) Standardized Rehabilitation Therapy will reduce biomarkers of inflammation; 4) Standardized Rehabilitation Therapy will decrease hospital costs. We will conduct a two-arm, randomized trial in 326 patients with ARF to compare Standardized Rehabilitation Therapy, initiated in the ICU and administered throughout the hospitalization, vs. Usual Care (control). Standardized Rehabilitation Therapy will consist of: passive range of motion, physical therapy and progressive resistance exercise (strength training). Our unique environment provides a hospital-funded, experienced Mobility Team (7days/week) consisting of a critical care nurse, physical therapist and nursing assistant to administer this protocol. The proposed study is a natural extension of our prior work, is multidisciplinary (Exercise Physiology, Physical Therapy, Nursing, Medicine, Basic Science, Health Economics), is supported by extensive preliminary studies, is innovative, and is responsive to recent society consensus statements. PUBLIC HEALTH RELEVANCE: For patients with ARF, no national standard for the administration of in-hospital rehabilitation exists. Patients with ARF suffer for months after hospital discharge with weakness and decreased quality of life. This study will provide the information for US hospitals to prioritize and budget for the rehabilitation needs of patients with ARF by demonstrating that Standardized Rehabilitation Therapy, initiated in the ICU, reduces hospital stay with immediate and sustained improvement in function and quality of life for patients with ARF.